Tang Lu, Guo Dingyuan, Jia Dongye, Piao Songlan, Fang Chunqiu, Zhu Yueya, Wang Yinghang, Pan Zhi
Fangzheng Research Laboratory, Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, China.
Department of Traditional Chinese Internal Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Front Med (Lausanne). 2024 Oct 4;11:1475239. doi: 10.3389/fmed.2024.1475239. eCollection 2024.
Rheumatoid arthritis (RA) is a widespread chronic autoimmune disease that primarily causes joint inflammation and damage. In advanced stages, RA can result in joint deformities and loss of function, severely impacting patients' quality of life. The "Tianyu" pair (TYP) is a traditional Chinese medicine formulation developed from clinical experience and has shown some effectiveness in treating RA. However, its role in the complex biological mechanisms underlying RA remains unclear and warrants further investigation.
We obtained gene sequencing data of synovial tissues from both RA patients and healthy individuals using two gene microarrays, GSE77298 and GSE55235, from the GEO database. Through an integrated approach involving bioinformatics, machine learning, and network pharmacology, we identified the core molecular targets of the "Tianyu" medicine pair (TYP) for RA treatment. Liquid chromatography-mass spectrometry was then employed to analyze the chemical components of TYP. To validate our findings, we conducted animal experiments with Wistar rats, comparing histopathological and key gene expression changes before and after TYP treatment.
Our data analysis suggests that the onset of RA may be associated with inflammation-related immune cells involved in both adaptive and innate immune responses. Potential key targets for TYP treatment in RA include AKR1B10, MMP13, FABP4, NCF1, SPP1, COL1A1, and RASGRP1. Among the components of TYP, Kaempferol, Quercetin, and Salidroside were identified as key, with MMP13 and NCF1 showing the strongest binding affinity to these compounds. Animal experiments confirmed the findings from bioinformatics and network pharmacology, validating the key targets and therapeutic effects of TYP in treating RA.
Our study reveals that TYP has potential clinical value in the treatment of rheumatoid arthritis. This research enhances our understanding of RA's pathogenesis and provides insight into potential therapeutic mechanisms.
类风湿关节炎（RA）是一种广泛存在的慢性自身免疫性疾病，主要导致关节炎症和损伤。在疾病晚期，RA可导致关节畸形和功能丧失，严重影响患者的生活质量。“天愈”药对（TYP）是一种基于临床经验研发的中药配方，在治疗RA方面已显示出一定疗效。然而，其在RA复杂生物学机制中的作用仍不明确，值得进一步研究。
我们使用来自GEO数据库的两个基因芯片GSE77298和GSE55235，获取了RA患者和健康个体滑膜组织的基因测序数据。通过生物信息学、机器学习和网络药理学相结合的方法，我们确定了“天愈”药对（TYP）治疗RA的核心分子靶点。随后采用液相色谱 - 质谱联用技术分析TYP的化学成分。为验证我们的研究结果，我们用Wistar大鼠进行了动物实验，比较TYP治疗前后的组织病理学和关键基因表达变化。
我们的数据分析表明，RA的发病可能与参与适应性和先天性免疫反应的炎症相关免疫细胞有关。TYP治疗RA的潜在关键靶点包括AKR1B10、MMP13、FABP4、NCF1、SPP1、COL1A1和RASGRP1。在TYP的成分中，山奈酚、槲皮素和红景天苷被确定为关键成分，MMP13和NCF1与这些化合物的结合亲和力最强。动物实验证实了生物信息学和网络药理学的研究结果，验证了TYP治疗RA的关键靶点和治疗效果。
我们的研究表明，TYP在类风湿关节炎治疗中具有潜在的临床价值。这项研究加深了我们对RA发病机制的理解，并为潜在的治疗机制提供了见解。
